Safety and Efficacy of Transcatheter Edge-to-Edge Repair for Atrial Functional Mitral Regurgitation (STAR)

Safety and Efficacy of Transcatheter Edge-to-Edge Repair for Atrial Functional Mitral Regurgitation - The STAR Trial

This study is a prospective, randomized, parallel-control, open-label, multicenter clinical trial. Eligible subjects will be randomized in a 1:1 ratio to the Device group (Interventional group) or to no Device group (Control Group). The objective is to identify the safety and effectiveness of the TEER for the treatment of moderate-to-severe (3+) or severe (4+) atrial functional mitral regurgitation (aFMR) in patients who are symptomatic despite maximally tolerated guideline directed medical therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Atrial Functional Mitral Regurgitation
• Intervention / Treatment: Device: Transcatheter Edge-to-Edge Repair

Detailed Description

Atrial functional mitral regurgitation (AFMR) is a complex cardiovascular condition typified by mitral regurgitation (MR), primarily due to atrial fibrillation-induced or diastolic dysfunction-induced left atrial enlargement, with mitral annular dilation and functional alterations of the mitral valve, rather than intrinsic valvular defects, resulting in regurgitation1. The reported prevalence of AFMR varies across studies, attributable to discrepancies in definitions, diagnostic techniques, research designs, and the specific populations investigated2-8. In a cohort study of hospitalized patients undergoing atrial fibrillation ablation, the prevalence of moderate or severe AFMR was 7%1. Conversely, in a community-based screening cohort of patients with moderate or severe MR, AFMR accounted for 27% of cases, marginally lower than the proportions of ventricular functional mitral regurgitation (VFMR, 38%) and primary mitral regurgitation (PMR, 32%)9. It can be anticipated that with the acceleration of aging in the global population, the proportion of AFMR may witness a considerable expansion in the future.

Compared with PMR, patients with AFMR frequently present with greater symptoms, diminished exercise tolerance, and heightened risk for hospitalization due to heart failure and increased mortality9,10, underscoring AFMR as a challenging therapeutic scenario. The conventional management strategies for mitral regurgitation have proven less effective in cases of AFMR2,11,12, due to its unique pathophysiological mechanisms, highlighting the imperative for customized treatment modalities.

Optimized guideline-directed medical therapy (GDMT) has been the cornerstone of treatment for heart failure and associated valvular diseases, including AFMR13. GDMT for heart failure with reduced LVEF typically includes a combination of a beta-blockers, ACE inhibitor, angiotensin receptor blockers or ARNI, a mineralocorticoid receptor antagonist, an SGLT2 inhibitor, and diuretics, along with anticoagulation for atrial fibrillation and cardiac resynchronization therapy for specific patients. However, the effectiveness of GDMT in treating AFMR specifically in whom the LVEF is typically preserved (≥50%) is not well-established14, as most prior studies have focused on PMR or heart failure with reduced ejection fraction. From the pathophysiological perspective of AFMR, strategies that restore sinus rhythm from atrial fibrillation have the potential to improve the prognosis of AFMR. Atrial fibrillation cardioversion may reduce the severity of MR, restore atrial size, enhance cardiac diastolic function, and decrease the incidence of endpoint events15-19. Transcatheter edge-to-edge repair (TEER) has emerged as a promising intervention for MR, in all patients with ventricular FMR and in those with PMR who are at high or prohibitive surgical risk14,20-22. Recent studies have demonstrated the efficacy of TEER in reducing the severity of MR, improving symptoms, and enhancing quality of life in patients with secondary MR23-25. However, its role in AFMR, a subset of secondary MR, is less clear.

Given the distinct pathophysiology of AFMR and the lack of consensus on optimal management, there is a pressing need for clinical trials comparing the efficacy of TEER versus GDMT in this patient population. Such trials are crucial for informing clinical practice and guiding treatment decisions in AFMR. This clinical trial aims to compare the efficacy and safety of TEER and GDMT in the management of AFMR, filling a significant knowledge gap in current research and potentially influencing future guidelines and patient care strategies.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sanshuai Chang, M.D.; Phone Number: +8618501369869; Email: 18501369869@163.com
• Study Contact Backup: Name: Guangyuan Song, M.D.; Phone Number: +8613801120805; Email: songgy_anzhen@vip.163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100000
      • Interventional Center of Valvular Heart Disease, Beijing Anzhen Hospital
      • Contact: Sanshuai Chang, M.D.; Phone Number: +8618501369869; Email: 18501369869@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 years or older

2. Echocardiographic core laboratory criteria (all must be present):

   1. Atrial FMR (FMR must be atrial in etiology without ventricular leaflet tethering)
   2. Severe MR (3+ or 4+) defined as either 1) an effective regurgitant orifice area (EROA) ≥0.3 cm² or pulmonary-venous systolic flow reversal (PSVFR), or 2) in the absence of PSVFR, EROA measures 0.20-0.29 cm² with one or more of the following: regurgitant volume ≥45 mL/beat, regurgitant fraction ≥40%, or vena contracta width ≥0.5 cm.
   3. LV ejection fraction ≥50% without more than mild regional wall motion abnormalities
   4. No or mild LV dilatation (LV end-diastolic volume index <79 mL/m2 [male] or <71 mL/m² [female])
   5. Left atrial dilation (left atrial volume index ≥34 mL/m²)
   6. Mitral annulus dilatation (AP diameter >35mm)

3. The mechanism of the atrial FMR is likely either atrial fibrillation (persistent/permanent or paroxysmal [documented]) and/or HFpEF. If HFpEF, one or both of the following must also be present:

   1. TTE criteria of diastolic dysfunction i. Average E/e' ≥15, or ii. Average E/e' 9-14 plus both of the following:

1. Septal e' <7 cm/s or lateral e' <10 cm/s 2. TR Vmax >2.8 m/s (or PASP >35 mmHg if TR jet is adequate) AND/OR b) Invasive hemodynamic evidence (measured prior to randomization) of elevated LV filling pressures (PCWP (or LVEDP) ≥15 mmHg at rest or ≥25 mmHg with exercise; Note: If PCWP is 12 to 15 mmHg, the patient may be given a 7-10 mL/kg (approximately 500 mL) rapid infusion (over 5-10 min) of normal saline; if PCWP rises to ≥18 mmHg, the subject may be randomized.

4. NT-proBNP ≥300 pg/mL (or BNP ≥100 pg/mL) if at the time of the test the patient is in sinus rhythm or NT-proBNP ≥600 pg/mL (or BNP ≥200 pg/mL) if the patient is in atrial fibrillation 5. Subject remains symptomatic (NYHA class II, III or ambulatory IV) despite maximally tolerated doses of societal indicated class I GDMT for ≥2 months

a) Diuretics as needed to treat pulmonary congestion and peripheral edema b) If atrial fibrillation: Rate control medication to ensure heart rate <110 bpm c) If HFpEF: i. SGLT2i for at least 2 months (required) ii. MRAs, e.g., spironolactone or finerenone) and angiotensin receptor-neprilysin inhibitors (ARNIs, e.g., sacubitril/valsartan) may be used at the discretion of each center (but should not be changed after randomization) 6. SBP <140 mmHg and HR <100 bpm (<110 bpm if in atrial fibrillation) 7. Atrial fibrillation ablation is determined by the local heart team. If ablation is deemed necessary, it will be performed prior to enrollment; if ablation is considered unsuitable, no ablation will be performed after enrollment.

8. Anatomy suitable for TEER 9. The subject or legal guardian voluntarily agrees to comply with all provisions of this clinical trial, including the possibility of being randomly assigned to the control group, as well as participating in all necessary postoperative follow-ups and provides written informed consent.

Exclusion Criteria:

1. Patient is clinically unstable or has been hospitalized within the prior 30 days.
2. Primary degenerative or organic mitral valve disease such as prolapse, Barlow's disease, rheumatic heart valve disease causing leaflet thickening, leaflet clefts or perforation, endocarditis, etc. Note: A small amount of mitral leaflet thickening or other abnormality may be present, but it cannot be the primary cause of MR.
3. Moderate or severe mitral annular calcification, or any degree of mitral annular calcification if it is the primary cause of the MR or would interfere with TEER.
4. Mitral valve area (MVA) <4.0 cm² or mean trans-mitral valve gradient >4 mmHg.
5. Intent to treat the patient with mitral valve surgery within the next 24 months if randomized to control
6. Known cardiomyopathy such as amyloid, sarcoid or hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, or pericardial diseases such as constrictive pericarditis.
7. Previous mitral valve surgery or transcatheter mitral valve intervention.
8. Any severe valvular disease of the pulmonary valve or tricuspid valve, or moderate or severe disease of the aortic valve.
9. Moderate or severe right ventricular dysfunction, defined as TAPSE≤14mm or RVFAV≤30% on the baseline echo.
10. Severe pulmonary hypertension defined as RVSP≥70mmHg on the baseline echo.
11. AF ablation procedure within 2 months prior to enrollment.
12. Any implantation of an intracardiac pressure monitoring system, baroreceptor activation therapy, cardiac contractility modulation within 2 months prior to enrollment or planned any time after enrollment.
13. If taking a chronic oral anticoagulation: Inability to discontinue it for several days prior to the procedure
14. If not taking a chronic oral anticoagulation: Inability to tolerate aspirin or clopidogrel for 6 months
15. Untreated clinically significant coronary artery disease requiring revascularization
16. Coronary artery bypass grafting (CABG) within prior 30 days
17. Percutaneous coronary intervention (PCI) within prior 30 days
18. Acute cerebrovascular event within prior 30 days or any prior intracranial hemorrhage
19. Allergic to heparin or any study drug that cannot be pre-medicated
20. Any contraindication to transesophageal echocardiography
21. IVC filter in place
22. Any atrial septal pathology interfering with mitral TEER (e.g. atrial septal aneurysm, device in place across the atrial septum, etc.)
23. Any major surgery within prior 30 days or anticipated within 24 months
24. Non-cardiac disease with a life expectancy <24 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Device group (Interventional group); Patients will receive transcatheter edge-to-edge repair for atrial functional mitral regurgitation plus maximally tolerated guideline-directed medical therapy for cardiovascular disease	Device: Transcatheter Edge-to-Edge Repair; The intervention to be implemented in this clinical study is Transcatheter Edge-to-Edge Repair (TEER), a minimally invasive, image-guided interventional procedure specifically designed for the treatment of mitral regurgitation (MR)
No Intervention: no Device group (Control Group); Patients will receive maximally tolerated guideline-directed medical therapy for cardiovascular disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first occurrence of a composite event of death from any cause, hospitalization for [worsening] heart failure or unplanned outpatient [worsening] heart failure event within 24 months	Time to first occurrence of a composite event of death from any cause, hospitalization for [worsening] heart failure or unplanned outpatient [worsening] heart failure event within 24 months; Hospitalization for heart failure requires an admission to an in-patient unit or an emergency room stay for ≥24 hours (or <24 hours if subject dies in the emergency room).; Outpatient worsening heart failure requires an unplanned visit to a doctor's office, urgent care center or emergency room visit with stay <24 hours.; Worsening heart failure must be present for both conditions, the definition of which requires all three of the following to be present:Deterioration of HF symptoms: at least 1 of the following symptomsDeterioration of HF signs: 2 physical examination findings or 1 physical examination + 1 laboratory or invasive findingUrgent escalation of therapy	From enrollment to the end of treatment at 24 months
Number of participants with the primary safety endpoint (device group only)	Primary safety endpoint is the composite of the following events within 30 days; Stroke; Myocardial Infraction; Single-Leaflet Device Attachment (SLDA); ECL-confirmed mitral stenosis requiring surgery; Any device-related complication requiring nonelective cardiovascular surgery; Durable left ventricular assist device (LVAD) implant; Heart transplantation	From enrollment to the end of treatment at 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with hospitalization for [worsening] heart failure or outpatient [worsening] heart failure events	All hospitalization for [worsening] heart failure or outpatient [worsening] heart failure events at 24 months	From enrollment to the end of treatment at 24 months
Number of participants with all-cause death	All-cause mortality at 24 months	From enrollment to the end of treatment at 24 months
Degree of MR reduction	MR reduction from baseline to 30 days, 12 months and 24 months	From enrollment to the end of treatment at 24 months
Rate of MR severity of 1+ or less	MR severity of 1+ or less at 30 days, 12 months and 24 months	From enrollment to the end of treatment at 24 months
Rate of MR severity of 2+ or less	Rate of MR severity of 2+ or less at 30 days, 12 months and 24 months	From enrollment to the end of treatment at 24 months
Degree of NYHA functional class change	Degree of NYHA functional class change from baseline to 6 months, 12 months and 24 months	From enrollment to the end of treatment at 24 months
Improvement in Kansas City Cardiomyopathy Questionnaire score (0-100, higher scores indicate a better outcome）	Improvement in KCCQ score from baseline to 6 months, 12 months and 24 months	From enrollment to the end of treatment at 24 month
Improvement in 6-minute walk distance	Improvement in 6-minute walk distance from baseline to 6 months, 12 months and 24 months	From enrollment to the end of treatment at 24 months
Reduction in left atrial volume index	Reduction in LAVI from baseline to 12 months and 24 months	From enrollment to the end of treatment at 24 months
Number of participants with a secondary safety endpoint (device group only)	Secondary safety endpoint is a composite of stroke, myocardial infraction, non-elective cardiovascular surgery for device related complications, durable LVAD implant or heart transplantation	From enrollment to the end of treatment at 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
MR Severity Grade	The echocardiographic endpoints will be reported at baseline, 30 days, 6 months, 12 months, 24 months, 3 years and 5 years:	From enrollment to the end of treatment at 5 years
Regurgitant Volume	The echocardiographic endpoints will be reported at baseline, 30 days, 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Regurgitant Fraction	The echocardiographic endpoints will be reported at baseline, 30 days, 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Left Ventricle End Diastolic Volume (LVEDV)	The echocardiographic endpoints will be reported at baseline, 30 days, 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Left Ventricular End Systolic Volume (LVESV)	The echocardiographic endpoints will be reported at baseline, 30 days, 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Left Ventricular End Diastolic Dimension (LVEDD)	The echocardiographic endpoints will be reported at baseline, 30 days, 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Left Ventricular End Systolic Dimension (LVESD)	The echocardiographic endpoints will be reported at baseline, 30 days, 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Left Ventricular Ejection Fraction (LVEF)	The echocardiographic endpoints will be reported at baseline, 30 days, 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Right Ventricular Systolic Pressure (RVSP)	The echocardiographic endpoints will be reported at baseline, 30 days, 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Mitral Valve Area	The echocardiographic endpoints will be reported at baseline, 30 days, 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Mitral Valve Gradient	The echocardiographic endpoints will be reported at baseline, 30 days, 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Left atrial strain	The echocardiographic endpoints will be reported at baseline, 30 days, 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Left ventricular strain	The echocardiographic endpoints will be reported at baseline, 30 days, 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Right ventricular strain	The echocardiographic endpoints will be reported at baseline, 30 days, 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
All-cause death	The clinical endpoints will be reported at 30 days and 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Cardiovascular death	The clinical endpoints will be reported at 30 days and 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Non-cardiovascular death	The clinical endpoints will be reported at 30 days and 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Hospitalization for [worsening] heart failure or outpatient worsening heart failure events	The clinical endpoints will be reported at 30 days and 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Hospitalizations for [worsening] heart failure	The clinical endpoints will be reported at 30 days and 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Outpatient [worsening] heart failure events	The clinical endpoints will be reported at 30 days and 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Durable LVAD or heart transplantation	The clinical endpoints will be reported at 30 days and 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
NYHA Functional Class	The clinical endpoints will be reported at 30 days and 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
6-minute walk distance (6MWD)	The clinical endpoints will be reported at 30 days and 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Kansas City Cardiomyopathy Questionnaire score (0-100, higher scores indicate a better outcome）	The clinical endpoints will be reported at 30 days and 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Mitral valve surgery (including type of surgery)	The clinical endpoints will be reported at 30 days and 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
New use of CRT	The clinical endpoints will be reported at 30 days and 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Durable LVAD implant	The clinical endpoints will be reported at 30 days and 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Heart transplantation	The clinical endpoints will be reported at 30 days and 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Repeat TEER (including reason for re-intervention)	The clinical endpoints will be reported at 30 days and 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Responder analysis for 6 Minutes Walk Distance, where responder is defined as alive and experiencing an improvement of 25 meters and 50 meters (difference in proportion of responders between Device and Control groups).	The clinical endpoints will be reported at 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Responder analysis for left atrial volume Index, where responder is defined as alive and experiencing an improvement of ≥5 mL/m2 (difference in proportion of responders between Device and Control groups)	The clinical endpoint will be reported at 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Responder analysis for Left Ventricular End Diastolic Volume Index, where responder is defined as alive and experiencing an improvement of ≥12 mL/m2 (difference in proportion of responders between Device and Control groups)	The clinical endpoints will be reported at 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Responder analysis for Kansas City Cardiomyopathy Questionnaire score, where responder is defined as alive and experiencing an improvement of ≥5 points (difference in proportion of responders between Device and Control groups)	The clinical endpoints will be reported at 6month, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years
Each subscale for Kansas City Cardiomyopathy Questionnaire score (difference in means between Device and Control groups)	The clinical endpoints will be reported at 6 months, 12 months, 24 months, 3 years and 5 years	From enrollment to the end of treatment at 5 years

Collaborators and Investigators

• Sponsor: Beijing Anzhen Hospital
• Investigators: Principal Investigator: Guangyuan Song, M.D., Beijing Anzhen Hospital; Principal Investigator: Gregg W. Stone, M.D., Academic Affairs for the Mount Sinai Heart Health System

Study record dates

Study Major Dates

• Study Start (Estimated): February 25, 2026
• Primary Completion (Estimated): February 25, 2030
• Study Completion (Estimated): February 25, 2030

Study Registration Dates

• First Submitted: February 5, 2026
• First Submitted That Met QC Criteria: February 10, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: atrial fibrillation; mitral regurgitation; heart failure with preserved ejection fraction; transcatheter edge-to-edge repair
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Heart Valve Diseases; Pathological Conditions, Signs and Symptoms; Atrial Fibrillation; Mitral Valve Insufficiency
• Other Study ID Numbers: BeijingAnzhen20260110; 2026 (Capital Health Development Research Special Project)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No